Albert seaton and william



Patented Apr. 1%, i927.

pairs-n stares resales rarest caries.

ALBERT SEATON AND WILLIAM O. RADER, 01 INDIANAPQLIS, INDIANA, ASSIGNORS TO ELI LILLY AND COMPANY, OF INDIANAPOLIS, INDIANA, A CORPORATION OF No Drawing. Application filed June 4,

In making physical examinations of individuals for various purposes, especially in connection with examinations for life insurance, a most desirable test and one that is rapidly growing in use is the sugar-tolerance test. By thus (.letermining the tolerance which the subject has for sugar, any tendency toward diabetes mellitus will be disclosed.

The test consists in having the patient take a specilied quantity oit' sugar, desirably glucose, usually in water solution, and making an examination of a specimen of his urine taken a definite time aft-er the ingestion of the sugar, to determine how much if any of the sugar passed through into the urine. Such a test is not new with us, but has been recognized as desirable for. some time.

However, certain psychological difficulties frequently arise in connection with the malting of such a test. The specimen of urine may not be obtained within a suitable time after the ingestion of sugar, whether by accident or intent. For various reasons the person being examined may not retain the sugar administered to him; or he may not take the sugar at all, although he was instructed to do so and may say that he did it. Because of the various personal equations thus involved, and of the fact that the taking of the sugar and the obtaining of the specimen of urine are necessarily some distance apart in time and necessarily largely or wholly under the control of the person being examined, and because the specimen obtained .must :t'retpiently be shipped to a distant point for examination (as to the home otlice of an insurance company), the sugar-tolerance test as heretofore made has not been reliable. An insurance company, for instance, has not been able to tell that an applicant for insurance actually took the required sugar, or that he retained it, or that the specimen of urine was obtained at the proper time after the sugar was taken. In consequence, the truth was hard to find.

It is the object of our inventioi'i to make the truth of the situation easier to find. To that end, it our object to provide a positive indication of these various things which were always doubtful heretofore, such as Whether or not the sugar was taken and retaned, and whether or not the specimen of TESTING SUGAR TOLERANCE,

1926. Serial No. 113,811.

urine was obtained at the proper time; and to provide this indication in the specimen itself, so that the chemist at the home oflice of the insurance company can positively determine the facts of this situation.

To that end, more specifically stated, it is the object of our invention to provide a sugar (desirably glucose) containing a substance which will have the following characteristics 1. Solubility at least as great as that of the sugar used.

Non-discoverability by the whether by color, taste, or smell.

3. Freedom from chemical reaction with the sugar used, whether rapidly or slowly.

l. Physiological inertness.

5. Certainty of passing through into the urine within a certain time after being taken.

6. Freedom from chemical reaction, whether rapid or slow, with the urine itself or the usual preservativesused therefor.

7. Freedom from any chemical reaction that would interfere with any quantitative or qualitative urinary test, as for albumin or sugar.

8. Suflicient cheapness so thatit can be placed in all specimens of sugar to be .administered, whether it is to be tested for or not.

9. Responsiveness to a practical and simple test for its presence in the urine.

lVe have found that we can obtain these results by providing a suitable indicator in subject,

the sugar which is administered to the subject. One such suitable indicator substance is soluble saccharin, or sodium benzosulphinide.

A very small proportion of this saccharin mixed with the glucose to be administered is found to fulfill all the necessary requirements. Vie find that one part of saccharin in from 1000 to 2000 parts of glucose gives excellent results, although no precise pro portions are essential to our invention. A convenient proportion is one grain of saccharin per 100 grams of glucose; and as 100 grams of glucose in 8 ounces of water is the usual quantity administered for the sugar-tolerance test, that means the administration of 1 grain of saccharin in making the test.

In addition, we may add some flavoring Hit) ested insurance company.

extract to the. glucose, such as Wintergreen, to make the taking of the glucose less distastefulas it isfound that the taking of 100gra1ns of unflavored glucose in 8 ounces of water is ('listas'teful .to many people. he presence or absence of the flavor is merely incidental,however, and has nothing to do with our invention. I y

Upon administration of this saceharincontaining glucose, a sufficient time is :a'llowed, and the urine specimen is obtained.

-Lf the time proper, usually from two to three hours after .1ngestio111,:the saccharin will appear in the urine; but ifthe time is not proper, the saccharin 'will not appem Sugar in various formsand quantities may appear in the urine, according to the tolcr- -ance of the individual for the sugar.

The presence of the saccharin' in the glucose does not .ariiect thephysiological .action of the glucose, or any other physiological function which is involved in urinary tests. The saccharin cannot be detected in the gluroseby color, taste, or smell, and does :not

reactat all with the glucose.

W'Vhen the specimen of urine is obtained, any usual preservative is .added, and :the specin'ien sent to 2tl1e h0me office of the interdoes notreact on any usual preservative, and does not interfere with any of the usual uni-nary tests.

The presence of the saccharin in the urine may be determined by a Iknown and relatively simple test, which does not greatly interfere with the other work of tlieanalyst, and does not require extended close watching. The reaction is distinct, and there is small chance -of :error. The :test which we prefer to useforthe presenee-ofthe saccharin in -the :urine is follows:

A small quantity of the urine to be tested is acidified slightly with phosphoric acid; and is then evaporated down toazthic'kspas'te, with care that :none of the paste is lost toward the last Eby excessive heating. This paste is extracted avith several smallport-ions of ether, and "the ether extracts are filtered oil, and the several other extracts are combined and evaporated to thickness over :a water bath. The residue is trz znsferred to a test tube, a pinch of dry .resorcin is added, and then a few drops of concentrated sulphuric acid are added. This'is heated until the mass begins :to swell, and "is then cooled until action ceases. This heating and cooling is desirably repeated several times. After the final cooling, 'the .material as diluted with 'water, and neutralized with The saccharin sodium hydroxide. At the .neutralpoint, a.

cred-green :fluorescence gives 1a IJOSlflVG indication of the presence of saccharm; while the absence of such fluorescence indicates "that saccharin "was not present, and thus indica'tes that the subject "(usually an up plicant for insurance) did not take-=01 re- .tainthe sugar furnished him, or that the specimen of urine was not obtained at the required time :after the ingestion of the sugar.

lVe claim as'ou-r invention.:

7 l. The process of testing an individual for sugar tolerance, whichconsists .in .administering a quantity of sugar mixed with a small amount of an'indicator which will appear in the urine within a definite, time after ingestion but which is not apparent .to the individual being tested, obtaining the urinary specimen, and testing it for the presence of sugar and for the presence of gSlICll indicator.

.2. The processrof/testing an individual for s. gar tolerance as set forth .in claim 1, with the addition that the indicator is sacharin.

3-3. A substance for use .in .making sugartolerance tests on individuals, comprising a mixture of sugar with :an indicator which will appear in the urine wi-hin a definite time after ingestion of the mixture, hut =whichzis not apparent to the individual be ing tested.

4. A substance for use in making sugartolerance tests on individuals, con'lprisiirg a :mixture of sugar with an indicator which will appear in the vurine within a definite time after ingestion of the mixture and which does not interfere with the usual urinary tests, but which is not apparent to :the individual being tested.

.A-su'bstance for use in making .sugartolerance tests on individuals, comprising a :ll'llXiZlll-G of sugar with an indicator which will appear in the urine within a definite time :after ingestion of the mixture and which does not interfere with the urinary test for sugar, but which is ,not a iparent ato the individual being tested.

6. A substance for use in making sugartolerance tests in individuals, comprising a mixture of sugar 'with a relatively small amount ofvsaccharin. V

In witness whereof, we have hereunto set our hands at ilndianapolis,Indiana, this 3rd day of June, A. .1). one thousandtninelhun- "dred and twenty-six.

ALBERT SEATON. TILLIAM "O "RADER. 

